Heterogeneous neurocognitive signatures in early childhood autism: a combined analysis of pharmacological treatment and gender

PURPOSE: Autism spectrum disorder (ASD) is characterized by marked heterogeneity in sensory processing, self-regulation, and executive functioning during early childhood. Pharmacological treatments are widely used to manage behavioral symptoms; however, their role in shaping multidomain neurocognitive profiles remains unclear. This study aimed to determine whether neurocognitive profiles differ as a function of pharmacological treatment type (antipsychotic, ADHD medication, or no medication) and gender children with ASD in early childhood. METHODS: This cross-sectional study included 350 children aged 4-6 years diagnosed with ASD. Participants were stratified into three groups based on current pharmacological treatment: antipsychotic-treated (n = 115), ADHD-medicated (n = 110), and medication-free (n = 125), with balanced gender distribution. Parents completed the Parent-Rated Sensory Reactivity Scale (ESRS), the Self-Regulation Skills Scale-Parent Form (SRSS-P), and the Childhood Executive Functioning Inventory-Parent Form (CEFI-P). Autism severity was assessed using the Childhood Autism Rating Scale (CARS). Group differences were examined using ANOVA, followed by correlation and multiple regression analyses. RESULTS: Neurocognitive profiles differed significantly across pharmacological treatment groups (p < 0.01). Children receiving antipsychotic medication exhibited higher sensory reactivity and greater autism severity, whereas those receiving ADHD medication showed greater impairments in executive functioning and self-regulation. Medication-free children consistently demonstrated the lowest levels of impairment. Gender showed a limited moderating effect, with some domain-specific differences observed across treatment groups. Correlation and regression analyses indicated that pharmacological treatment and gender were associated with variability in neurocognitive domains and overall autism severity (R² = 0.46). CONCLUSIONS: Pharmacological treatment type and gender are important factors associated with heterogeneity in neurocognitive profiles in early childhood (4-6 years) ASD. These findings suggest that medication-related differences extend beyond behavioral symptom control and are linked to distinct sensory, regulatory, and executive functioning patterns. Clinically, this highlights the importance of considering treatment type and gender when interpreting neurodevelopmental profiles and when planning individualized, multidomain interventions.